Mirabegron has the following chemical structural formula:
Mirabegron or a pharmaceutically acceptable salt thereof has a β3-adrenergic receptor agonist activity, and is known to be useful as a therapeutic agent for overactive bladder (Patent literatures 1 to 3). Tablets containing mirabegron have already been placed on the market, and are sold in Japan, as “Betanis (registered trademark) tablet 25 mg” and “Betanis (registered trademark) tablet 50 mg”.
It is known that the pharmacokinetics vary depending on the presence or absence of food intake in clinical studies conducted in the development phase of the mirabegron (Patent literature 4). When the pharmacokinetics vary depending on the presence or absence of food intake, inevitably, it affects its effects. Particularly in medicine, if an effect different from the prediction occurs, since it is considered that it may lead to unexpected situations, it is necessary to predict certain effects. Therefore, the development of a drug in which a variation in pharmacokinetics depending on the presence or absence of food intake is minimized is strongly demanded. It is known that the variation in pharmacokinetics depending on the presence or absence of food intake in mirabegron can be reduced by controlling the drug release using various additives (Patent literature 4).
The formulations that are currently placed on the market are tablets, and thus, development of various dosage forms, such as liquids and solutions or the like, is desired from the viewpoint of a patient's further drug dosing compliance, or the like.
As a modified release liquid, a pharmaceutical composition, such as granules (suspension) or the like, containing an alkyl sulfate of mirabegron, is known (Patent literature 5).
On the other hand, in the medical field, for example, a ready-to-suspend preparation is prepared in medical facilities, and it is brought back to a general household, and taken in accordance with dosage and administration. When a ready-to-suspend preparation is prepared in medical facilities, it is desirable that a suspension in which a thickener (for example, xanthan gum) is dissolved is prepared within an appropriate time. When the preparation is brought back to a household and taken, since the suspension is resuspended before medication, and a predetermined dose is divided, it is desirable to maintain the suspended state for an appropriate period of time.
When a ready-to-suspend preparation is suspended in a solvent, such as water, a thickener tends to be in a lumpy state, and since a thickener in the lumpy state is incompletely hydrated, the thickener may not be able to fully demonstrate its function.
For example, as a method of preventing xanthan gum from being in a lumpy state, in order to improve the development of viscosity and enhance solubility when xanthan gum is dissolved, an invention relating to a composition, wherein metal salts are bound to the surface of xanthan gum, and as a result, the dissolution of the surface is controlled by modifying the surface of xanthan gum, and the dispersion properties of xanthan gum in water are improved, is proposed (Patent literature 6).
In order to provide a viscous liquid, without forming undissolved lumps of powder, even at ordinary temperature, an invention relating to a powdery administration-assisting food containing an anionic polymer and a preventive agent of undissolved lumps of powder, such as sodium hydrogen carbonate or the like, is proposed (Patent literature 7).
A powdery composition containing a gelling agent for preparing sol-like or gel-like food, characterized by containing water-insoluble calcium-containing material powder, which functions as a preventive agent of undissolved lumps of flour, is disclosed (Patent literature 8).
However, Patent literatures 6 to 8 do not disclose mirabegron or a pharmaceutically acceptable salt thereof. Additionally, Patent literatures 6 to 8 disclose inventions relating to food, but do not disclose any inventions relating to medicaments.
Therefore, there is still room for improvement in providing a pharmaceutical composition containing mirabegron or a pharmaceutically acceptable salt thereof which does not generate undissolved lumps, even when a ready-to-suspend preparation is prepared using a solvent, such as water or the like.